Exposure to PM induces neurotoxicity, mitochondrial dysfunction, oxidative stress and inflammation in human SH-SY5Y neuronal cells.

Ambient air pollution is a global public health issue. Recent evidence suggests that exposure to fine aerosolized particulate matter (PM) as small as ≤2.5 microns (PM) is neurotoxic to brain structures. Many studies also suggest exposure to PM may cause neurotoxicity and affect brain function. However, the molecular mechanisms by which PM exerts these effects are not fully understood. Thus, we evaluated the hypothesis that PM exposure exerts its neurotoxic effects via increased oxidative and inflammatory cellular damage and mitochondrial dysfunction using human SH-SY5Y neuronal cells. Here, we show PM exposure significantly decreases viability, and increases caspase 3 and 9 protein expression and activity in SH-SY5Y cells. In addition, PM exposure decreases SH-SY5Y survival, disrupts cell and mitochondrial morphology, and significantly decreases ATP levels, D-loop levels, and mitochondrial mass and function (maximal respiratory function, COX activity, and mitochondrial membrane potential) in SH-SY5Y cells. Moreover, SH-SY5Y cells exposed to PM have significantly decreased mRNA and protein expression levels of survival genes (CREB and Bcl-2) and neuroprotective genes (PPARγ and AMPK). We further show SH-SY5Y cells exposure to PM induces significant increases in the levels of oxidative stress, and expression levels of the inflammatory mediator's TNF-α, IL-1β, and NF-κB. Taken together, these results provide the first evidence of the biochemical, molecular and morphological effects of PM on human neuronal SH-SY5Y cells, and support our hypothesis that increased mitochondrial disruption, oxidative stress and inflammation are critical mediators of its neurotoxic effects. These findings further improve our understanding of the neuronal cell impact of PM exposure, and may be useful in the design of strategies for the treatment and prevention of human neurodegenerative disorders.